Cancer Immunology, Immunotherapy

, Volume 61, Issue 10, pp 1671–1682

Intratumoral electroporation of IL-12 cDNA eradicates established melanomas by Trp2180–188-specific CD8+ CTLs in a perforin/granzyme-mediated and IFN-γ-dependent manner: application of Trp2180–188 peptides

  • Jeong-Im Sin
  • Jae-Bok Park
  • In Hee Lee
  • Daehan Park
  • Youn Seok Choi
  • Jongseon Choe
  • Esteban Celis
Original article

DOI: 10.1007/s00262-012-1214-8

Cite this article as:
Sin, JI., Park, JB., Lee, I.H. et al. Cancer Immunol Immunother (2012) 61: 1671. doi:10.1007/s00262-012-1214-8
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Abstract

Intratumoral electroporation (IT-EP) with IL-12 cDNA (IT-EP/IL12) can lead to the eradication of established B16 melanoma tumors in mice. Here, we explore the immunological mechanism of the antitumor effects generated by this therapy. The results show that IT-EP/IL12 applied only once resulted in eradication in 70% animals with large established B16 tumors. Tumor eradication required the participation of CD8+ T cells, but not CD4+ T cells and NK cells. IT-EP/IL12 induced antigen-specific CD8+ T cell responses against the immunodominant Trp2180–188 epitope and generated a systemic response, resulting in significant therapeutic effects against distal, untreated tumors. The therapeutic effect of IT-EP/IL12 was absent in perforin-deficient mice, indicating that tumor elimination occurred through conventional perforin/granzyme lysis by CTLs. Moreover, this therapy induced some degree of immunological memory that protected approximately one-third of the cured mice against a subsequent tumor challenge. Moreover, antitumor efficacy and long-term protection against B16 were significantly improved by concurrent Trp2 peptide immunization through more induction of Ag-specific CTL responses and more attraction of IFN-γ-expressing CD8+ T cells into tumor sites. The antitumor effect of IT-EP/IL12 required the participation of IFN-γ, which was shown to induce MHC class I expression on B16 cells and increase the lytic activity of the CD8+ CTL generated by IT-EP/IL12. The results from these animal studies may help in the development of IT-EP/IL12 for cancer patients.

Keywords

Antitumor immunity Electroporation IL-12 Melanoma 

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Jeong-Im Sin
    • 1
  • Jae-Bok Park
    • 2
  • In Hee Lee
    • 3
  • Daehan Park
    • 4
  • Youn Seok Choi
    • 5
  • Jongseon Choe
    • 1
  • Esteban Celis
    • 6
  1. 1.Department of Microbiology, School of MedicineKangwon National UniversityChuncheonKorea
  2. 2.Department of Pathology, School of MedicineCatholic University of DaeguNamguKorea
  3. 3.Department of Nephrology, School of MedicineCatholic University of DaeguNamguKorea
  4. 4.Department of Plastic Surgery, School of MedicineCatholic University of DaeguNamguKorea
  5. 5.Department of Obstetrics and Gynecology, School of MedicineCatholic University of DaeguNamguKorea
  6. 6.Immunology Program, Department of Oncologic Sciences, Moffitt Cancer CenterUniversity of South FloridaTampaUSA